MIT Department of Biology
7.013: Introductory Biology - Spring 2005
Instructors: Professor Hazel Sive, Professor Tyler Jacks, Dr. Claudette Gardel
7.013 Spring 2005 Problem Set 7 FRIDAY May 6th, 2005
Question 1
Bovine spongiform encephalopathy (BSE, also called mad cow disease) and other similar
diseases are caused by infectious particles called prions.
a) Prions are made of (circle one.)
Viruses
bacteria
DNA
RNA
protein
lipid
carbohydrate
b) True or false, if false correct the sentence:
T
F
T
F
T
T
F
F
Several new mutations arise in the brains of cows that become affected by BSE.
.
In BSE, viral factors convert proteins in the brain from one form to another.
BSE cannot be transmitted from one cow to another.
Spongiform encephalopathies cannot be transmitted from one species to another.
In yeast, there have been found prions that behave similarly to those that cause BSE. In the case of one
yeast prion, one protein conformation causes the cells to be white and another conformation causes them to
be red. This confers to colonies being red or white. Assume that the protein state analogous to the
infectious form of BSE causes the yeast to be red.
You grow these yeast and you notice that individual colonies are mostly of a single color, but small white
sectors arise within red colonies, and small red sectors arise within white colonies.
c) What causes red sectors to arise within white colonies?
d) If you took yeast from a red sector and replated them what color colonies would form and why?
e) What causes white sectors to arise within red colonies?
f) If you took yeast cells from a white sector and replated them, what color colonies would form and why?
Heat shock proteins help prevent the proteins present in cells from becoming aggregated and then
degraded when cells are exposed to high temperature. They do this by unfolding and then refolding these
proteins.
g) You find that when you express high levels of these heat shock proteins in red yeast cells (from above)
and replate the yeast, now they grow into white colonies. Provide a possible explanation for this.
Question 2
AIDS is an immunodeficiency disease caused by infection by a retrovirus called HIV.
a) What is the central dogma?
b) How do retroviruses violate this principle?
Viruses require host cells for propagation. Each virus has a specific host cell type that it
infects.
c) How are viruses able to specifically infect only one cell type?
d) What is the role of helper TH cells in the immune system?
e) What is the effect of loss of helper TH cells?
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Question 3
You have a new position at the Center for Disease Control. You have been assigned to
characterize a new epidemic that has spread rapidly among workers at a chicken farm in
California. All affected have high fever and a severe cough. A co-worker has given you a
purified vial of the infectious material.
a) You add some of the infectious material to an agar plate containing all necessary
nutrients, but nothing grows. Why is this?
b) You then add infectious material to a human cell line and see some cells begin to round
up and die.
i) What is the likely infectious material and why didn’t it grow on the agar plate?
The infectious material is a virus and it didn’t grown on the agar plate because virus
need host cells to replicate.
ii) If the cells were put into a tube with the media they grew in and spun down, Where
would you find the material that could infect new cells?
In the media/supernatant
In the pelleted cells
(iii) Why?
The virus that hasn’t exited the cells isn’t fully formed.
c) You isolate the genetic material if the virus and send a portion off for sequencing.
Your sequence contains Uracil instead of Thymadine and it seems it is a single stranded
genome.
i) How could you tell if this was a (+) or (-) sense RNA?
ii) You determined it was a (-) ssRNA. List the steps this virus must go through to
replicate.
Question 4
I. Order the steps below in the life cycle of AIDS
a) Viral RNA degrades
b) cDNA integrated into host genome
c) New virus buds from cell
d) Viral proviral DNA becomes double stranded
e) Viral RNA translated into protein
f) Viral envelope fuses with host cell plasma membrane
g) viral RNA produced from host genome
h) Reverse transcriptase makes cDNA
i) cDNA enters the nucleus
j) New viruses are assembled
k) HIV binds to CD4 proteins
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II. The figure below shows the structure of the AIDS virus and the genome of the virus
illustrating the essential genes.
Enzymes
(Reverse Transcriptase and others)
Protein Coat
Membrane
Envelope Protein
Genetic Material (RNA)
(
gag
gene
( (
pol
gene
(
(
env
gene
(
Figure by MIT OCW.
For each of the genes listed below explain what the function of the protein it encodes is:
gag gene
pol gene
env gene
III. Which steps of the AIDS life cycle would make good drug targets?
(1) Attachment and penetration of virus
(2) Reverse transcription
(3) Transcription and translation
(4) Viral Maturation, Transport & Packaging
(5) Assembly and release
IV. How could you make a drug targeting the host cell recognition step of the virus life
cycle?
V. Why is reverse transcriptase a good drug target?
VI. How do inhibitors of reverse transcriptase such as AZT work?
Question 5
Avian influenza virus is a flu virus that infects many species of birds, including both
livestock and migratory birds. The virus is highly mutable, giving rise to strains of high or
low pathogenicity. The more pathogenic strains of the virus can approach 100% mortality
in a very short period of time.
a) Is a more pathogenic form of this virus more likely appear on a commercial poultry
farm, or in a wild population of ducks?
b) Is the virus more likely to be spread worldwide by livestock or migratory birds?
c) Avian virus was identified in Italy, over 100 years ago. Human infection did not occur
until 1997. At a molecular level, why could it be difficult for avian virus to infect humans?
d) While studying avian flu in the lab, you notice that replication of the viral genome
happens using a very low fidelity polymerase. Could this confer any benefit to the virus?
What?
e) Given that there are indeed documented cases of human infection, what do you imagine
occurred to facilitate this?
f) Are humans more or less likely to contract avian flu from infected humans, or from
infected poultry?
g) What modern farm practices could lead to the prevalence of avian virus that can infect
humans?
h) Why don’t the high levels of antibiotics pumped into commercial poultry reduce the
incidence of avian flu?
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